Hollow-core photonic-crystal fibers optimized for four-wave mixing (FWM) and coherent anti-StokesRaman scattering (CARS) spectroscopy were designed and fabricated. These fibers provide maximum transmission for a two-color pump and the FWM signal, allowing FWM to be enhanced by a factor of ∼800 compared with the tight-focusing regime. A reliably detectable FWM signal was generated under these conditions with micro-and even submicrojoule picosecond pump pulses, i.e. at the level of pump energies unprecedentedly low for non-resonant FWM in the gas phase. The FWM efficiency is shown to depend on the relative orientation of polarization vectors of input pump pulses, offering the extension of FWM and CARS polarization techniques to air-guided modes in photonic-crystal fibers.